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Protalix BioTherapeutics and Chiesi Global Rare Diseases Announce Positive Topline Results from BRIGHT Phase III Open-Label, Switch-Over Clinical Trial Evaluating Pegunigalsidase Alfa 2 mg/kg every Four Weeks for Treatment of Fabry Disease
The BRIGHT study is a Phase III 12-month, open-label, switch-over study designed to evaluate the safety, efficacy and pharmacokinetics of PRX–102 treatment, 2 mg/kg every four weeks, in up to 30 patients with Fabry disease previously treated with a commercially available enzyme replacement therapy (ERT) (agalsidase alfa – Replagal® or agalsidase beta – Fabrazyme®), for at least three years and on a stable dose administered every two weeks.
Topline results indicate that 2 mg/kg of PRX–102 administered by intravenous infusion every four weeks was found to be well tolerated among treated patients, and stable clinical presentation was maintained in adult Fabry patients. No new patients developed treatment-induced anti-drug antibodies (ADA) following the switch to PRX–102 treatment.
"We are excited to share these topline results from the BRIGHT study, our third consecutive positive clinical trial of PRX–102, following the Phase I/II and the BRIDGE clinical studies. The results indicate that this investigational therapy is well tolerated and potentially an effective treatment for adult patients living with Fabry disease," said Einat Brill Almon, Ph.D., Protalix's Senior Vice President and Chief Development Officer. "We are encouraged to see that all of the patients who completed this study chose to enroll in the long-term extension study. Currently, 80% of the patients enrolled in the BRIGHT study have been treated with this treatment regimen for over two years. We look forward to advancing this study and further evaluating the results."
"These results demonstrate the potential of PRX–102 to be an important treatment option for the Fabry community and that the 2 mg/kg of PRX–102 every four weeks regimen may offer meaningful benefits to both patients and physicians. Treating physicians will be empowered with a potential additional treatment regimen, shown to be well tolerated, that they can offer to Fabry patients, pending approval of PRX-102," said Dror Bashan, Protalix's President and Chief Executive Officer. "We are gratified to have a strong balance sheet supporting our development efforts and look forward to executing and delivering on a year rich with value enhancing milestones."
The BRIGHT study enrolled 30 adult patients (24 males and 6 females). The most common Fabry disease symptoms were acroparesthesia, heat intolerance, angiokeratomas and hypohydrosis. All 30 patients received at least one dose of PRX–102, and 29 patients (mean [SD] age was 40.5 [11.3] years, ranging from 19 to 58 years) completed the 12-month study. Of these 29 patients, 28 received the intended regimen of 2 mg/kg every four weeks throughout the study, while one patient was switched to PRX–102 1 mg/kg every two weeks per protocol. One patient withdrew from the study after the first infusion due to a traffic accident.
Following screening, patients were enrolled and switched from their then current ERT to intravenous (IV) infusions of 2 mg/kg of PRX–102 every four weeks for 52 weeks (a total of 14 infusions). First infusions of PRX-102 were administered under controlled conditions at the investigation site. Based on the protocol-specified criteria, patients were able to receive their PRX-102 infusions at a home care setup once the Investigator and Sponsor Medical Monitor agreed that it was safe to do so. Safety and efficacy exploratory endpoints were assessed throughout the 52-week study.
Study outcome measures showed plasma lyso–Gb3 concentrations remained stable during the study with a mean change of 3.01 nM from baseline (19.36 nM) to Week 52 (22.23 nM). Mean absolute change of eGFR values were stable during the 52–week treatment period, with a mean change from baseline of –1.27 mL/min/1.73 m2.
"Patients participating in the BRIGHT study have expressed their satisfaction with the once every four weeks regimen," said
Following a survey of participants using the Quality of Life EQ-5D-5L questionnaire, responses indicate that patient perception of their own health remained high and stable throughout the 52–week study duration, with overall health mean (SE) scores of 78.3 (3.1) and 82.1 (2.9) at baseline and Week 52, respectively, in a 0 to 100 scale. Using the short-form Brief Pain Inventory (BPI) questionnaire, approximately 75% of study participants had an improvement or no change in average pain severity at Week 52 (compared to baseline). The short-form BPI interference items also remained stable during the study. Pain-related results indicate that there was no increase and/or relapse in pain. No Fabry clinical events were reported during the study.
"Of the 30 patients enrolled, 20 patients remained negative for anti-drug antibodies throughout the course of treatment. Of the 10 patients who were initially positive for anti-drug antibodies, four became negative for neutralizing antibodies at 12 months, suggesting tolerization by these patients," added
"On behalf of our team at Chiesi, we are grateful to the patients, families, and investigators for their time and participation in this study," said
The Company intends to report final data on the BRIGHT study in the second half of 2021, and to present these findings at an appropriate medical conference.
About Fabry Disease
Fabry disease is an X-linked inherited disease that results from deficient activity of the lysosomal α–Galactosidase–A enzyme resulting in progressive accumulation of abnormal deposits of a fatty substance called globotriaosylceramide (Gb3) in blood vessel walls throughout a person's body. Fabry disease occurs in one person per 40,000 to 60,000. Fabry patients inherit a deficiency of the α–Galactosidase–A enzyme, which is normally responsible for the breakdown of Gb3. The abnormal storage of Gb3 increases with time and, accordingly, Gb3 accumulates, primarily in the blood and in the blood vessel walls. The ultimate consequences of Gb3 deposition range from episodes of pain and impaired peripheral sensation to end-organ failure – particularly of the kidneys, but also of the heart and the cerebrovascular system.
PRX–102 (pegunigalsidase alfa) is an investigational, plant cell culture-expressed, and chemically modified stabilized version of the recombinant α–Galactosidase–A enzyme. Protein sub-units are covalently bound via chemical cross-linking using short PEG moieties, resulting in a molecule with unique pharmacokinetic parameters. In clinical studies, PRX–102 has been observed to have a circulatory half-life of approximately 80 hours. The Company designed PRX–102 to potentially address the continued unmet clinical need in Fabry patients.
About Chiesi Global Rare Diseases
Chiesi Global Rare Diseases is a business unit of the
To the extent that statements in this press release are not strictly historical, all such statements are forward-looking, and are made pursuant to the safe-harbor provisions of the Private Securities Litigation Reform Act of 1995. The terms "expect," "anticipate," "believe," "estimate," "project," "may," "plan," "will," "would," "should" and "intend," and other words or phrases of similar import are intended to identify forward-looking statements. These forward-looking statements are subject to known and unknown risks and uncertainties that may cause actual future experience and results to differ materially from the statements made. These statements are based on our current beliefs and expectations as to such future outcomes. Drug discovery and development involve a high degree of risk and the final results of a clinical trial may be different than the preliminary findings for the clinical trial. Factors that might cause material differences include, among others: failure or delay in the commencement or completion of our preclinical and clinical trials which may be caused by several factors, including: risks that the FDA will not accept an application for accelerated approval of PRX–102 with the data generated to date or will request additional data or other conditions of our submission of any application for accelerated approval of PRX–102; unforeseen safety issues; determination of dosing issues; lack of effectiveness during clinical trials; inability to monitor patients adequately during or after treatment; inability or unwillingness of medical investigators and institutional review boards to follow our clinical protocols; and slower than expected rates of patient recruitment; risks associated with the novel coronavirus disease (COVID–19) outbreak, which may adversely impact our business, preclinical studies and clinical trials; risks related to any transactions we may effect in the public or private equity markets to raise capital to finance future research and development activities, general and administrative expenses and working capital; the risk that the results of the clinical trials of our product candidates will not support our claims of safety or efficacy, that our product candidates will not have the desired effects or will be associated with undesirable side effects or other unexpected characteristics; risks related to our ability to maintain and manage our relationship with our collaborators, distributors or partners; risks related to the amount and sufficiency of our cash and cash equivalents; risks relating to our ability to make scheduled payments of the principal of, to pay interest on or to refinance our outstanding notes or any other indebtedness; our dependence on performance by third party providers of services and supplies, including without limitation, clinical trial services; delays in our preparation and filing of applications for regulatory approval; delays in the approval or potential rejection of any applications we file with the FDA or other health regulatory authorities, and other risks relating to the review process; the inherent risks and uncertainties in developing drug platforms and products of the type we are developing; the impact of development of competing therapies and/or technologies by other companies and institutions; potential product liability risks, and risks of securing adequate levels of product liability and other necessary insurance coverage; and other factors described in our filings with the U.S. Securities and Exchange Commission. The statements in this press release are valid only as of the date hereof and we disclaim any obligation to update this information, except as may be required by law.
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